Molecular recognition is not only central to signal transduction in living systems, but also represents the functional principle of pharmaceuticals and laboratory diagnostics. A variety of opportunities thus comes along with an in-depth understanding of biological binding events. From this perspective, it is not surprising to see an ever-growing interest in quantitative biomolecule interaction analysis. To this end, the directed movement of molecules along a temperature gradient, referred to as thermophoresis, has successfully been utilized in the last years. Thermophoresis measurements are highly sensitive to molecular size, charge, and/or conformation. At least one of these parameters is measurably influenced upon each biomolecular interaction. Based on this influence, affinity and/or concentration can be quantified, even in complex bioliquids.
In the well established microscale thermophoresis (MST) approach, which has successfully been commercialized by NanoTemper Technologies GmbH, samples are measured in glass capillaries. Capillary MST has been applied, for example, for ions, small molecules, nucleic acids, peptides, proteins, crude cell lysate, and untreated human blood serum. With about 0.5 μl per capillary filling, i.e., 0.5 μl handling volume, the sample consumption is low compared to, e.g., isothermal titration calorimetry.
It is also known that thermophoresis measurements can be carried out in small droplets with a volume in the range of μl. Such droplets could be produced by using micropipettes. It was also known to cover such μl droplets with oil to prevent evaporation.
The additionally consumed volume becomes essential when working with expensive or rare material, like patient samples. This is especially true if high-throughput analyses need to be performed, e.g., in diagnostics or drug discovery. Throughput and automation of conventional MST might be limited by the handling of glass capillaries.
The inventors of the present invention noted that there is a need for an improved technique for thermophoresis measurements. It is further noted that there is a need for a more efficient and/or more effective and/or faster technique for thermophoresis measurements.
Therefore, the present invention provides for an improved system and method for thermophoresis measurements in very small volumes, preferably very small droplets.
The objects of the invention are achieved by the features of the independent claims. Further preferred embodiments are characterized in the dependent claims.